Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0020437 (hypercalcemia)
 10,293 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Two cases of familial hypocalciuric hypercalcemia (FHH) are reported with a review of the literature. Both cases had hypercalcemia, hypophosphatemia, variable parathormone (PTH) levels and hypocalciuria. The parathyroid glands were only slightly hyperplastic and subtotal parathyroidectomy did not reduce the hypercalcemia. FHH is an autosomal dominant congenital disease with high penetrance. It is characterised by hypocalcemia. This contradictory biological finding should alert the physician to the diagnosis and initiate a familial enquiry. The serum PTH and urinary cyclical-AMP levels do not distinguish FHH from primary hyperparathyroidism. Surgery is usually contraindicated because it is ineffective and because the disease is usually benign. Semi-quantitative bone histology in a patient with a high PTH level was normal. The value of bone biopsy in these cases is discussed.
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PMID:[Familial hypocalciuric hypercalcemia: two case reports (author's transl)]. 711 60

A 70-year-old white woman had a lower abdominal mass and hypercalcemia. Physical and radiologic evidence was found for the presence of nonmetastatic pelvic tumor. Biochemical tests confirmed the presence of hypercalcemia with evidence of active bone resorption. Plasma parathyroid hormone (PTH) and the nephrogenic urinary cyclic AMP excretion were low; levels of plasma prostaglandins were elevated. Bone biopsy revealed histologic evidence of extensive osteoclastic bone resorption. At operation, a papillary serous cystadenocarcinoma of the ovary was removed. Postoperatively, the serum calcium fell to normal, and plasma prostaglandins became undetectable. Short-term incubation of ovarian tumor fragments demonstrated the production by tumor tissue of a substance causing bone resorption in an in vitro bioassay. The production of this substance was blocked by indomethacin. Radioimmunoassay of the incubation medium revealed significant amounts of prostaglandins of the E + F series. Parathyroid hormone was not detected in the medium. These data implicate tumor-produced prostaglandins as mediators of the hypercalcemia in this patient.
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PMID:Hypercalcemia with ovarian carcinoma: evidence of a pathogenetic role for prostaglandins. 727 55

A premenopausal woman with soft tissue metastases from a carcinoma of the breast developed hypercalcemia with hypophosphatemia, reduced tubular reabsorption of phosphate, elevated urinary cyclic AMP levels and normal serum PTH levels was observed. Hormonal therapy with testosterone followed by tamoxifen induced normalization of her serum calcium concomitant with the disappearance of the pleural effusion and reduction in the size of her lung metastases. The correlation between the efficacy of antitumor treatment on pleural effusion, lung metastases, and normalization of serum calcium, as well as the elevated PTH level in the pleural effusion, suggest that this breast carcinoma secreted a PTH-like substance.
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PMID:Hypercalcemia in carcinoma of the breast without evidence of bone destruction: beneficial effect of hormonal therapy. 729 87

Measurement of parathyroid hormone (PTH) is important for diagnosing hyper- and hypoparathyroidism. The move to two-site immunometric assays that detect the whole molecule has improved the discrimination of these conditions but these assays may be too restrictive because some PTH fragments that are biologically active may not be detected. In addition, PTH-like peptide of malignancy, an important cause of malignancy-associated hypercalcaemia, is not detected by the two-site assays. Experiments were performed to set up a simple, robust and inexpensive bioassay for PTH, exploiting a kidney cell line and using cyclic AMP or an eluted stain assay as the end point. Of the 12 cell lines tested, an opossum kidney (WOK) cell line showed the most promise. Despite optimization of the procedure to include pre-treatment with dexamethasone, insulin and PTH, followed by incubation in the presence of 5'-guanylimidodiphosphate, isobutyl-1-methylxanthine and forskolin, the WOK cells showed insufficient sensitivity for use in a cultured cell bioassay for PTH in human serum. In addition, the cells were less sensitive to PTH-like peptide precluding their use for an assay for this molecule.
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PMID:Studies on the use of cultured cells in a bioassay for parathyroid hormone. 782 91

Lithium has proved to be a highly effective preventive measure in mood disorders and an increasing number of patients are receiving long-term lithium carbonate therapy. Among other biologically and clinically important effects of lithium, the possible induction of hyperparathyroidism was first suggested in 1973 by Garfinkel et al. About thirty other case reports have since been described, but they could simply have represented the coincidental occurrence of primary hyperparathyroidism and lithium carbonate treatment in the same patients. Eleven cross-sectional studies of calcium metabolism in patients treated with lithium carbonate have been reported. Evidence of a causal relationship of lithium to hyperparathyroidism can lead to a loss of effectiveness of lithium in controlling the affective symptoms. Interestingly, coexistence with hypothyroidism is not uncommon. Low serum phosphate, high serum chloride are also observed. Bone mineral content may decrease. In addition, several studies have shown that lithium treatment increases serum magnesium level. Unusual metabolic features are associated with hyperparathyroidism and long-term lithium treatment: low urinary calcium excretion, absence of nephrolithiasis, and normal urinary cyclic AMP excretion. Lithium inhibition of PTH sensitive adenylcyclase in the kidney would explain these features. In vitro studies suggested that lithium is a potent inhibitor of several hormone responsive adenylcyclase systems. It is possible that the tissue susceptibility to adenylcyclase inhibition in an individual may decide the nature of endocrine dysfunction seen during lithium treatment. Information about the time course with which abnormalities may develop is derived from longitudinal studies. Several months to several years are needed for lithium inducing primary hyperparathyroidism. In vitro studies provide strong evidence that lithium can induce a shift in the set-point for inhibition of PTH secretion by calcium and a direct stimulation of PTH secretion. The extent to which we can extrapolate these data to the clinical situation is discussed. In vivo data from Shen an Seely are compatible with these two mechanisms. These alterations should cause parathyroid hyperplasia. The possibility that a generalized parathyroid stimulus might lead to formation of a single adenima is not proved. Several recommendations regarding parathyroid function in patients receiving lithium have been suggested. Measurement of total calcium and serum proteins or of serum calcium ion values when available should be performed before therapy is begun. If elevated values are obtained, lithium treatment should be deferred and evaluation for hyperparathyroidism performed. Serum calcium should be monitored periodically during lithium treatment. Sustained hypercalcemia or true hyperparathyroidism require parathyroidectomy. If hypercalcemia is mild without complication and psychiatric symptoms well controlled, perhaps surgery should not be employed.
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PMID:[Hyperparathyroidism with lithium]. 808 38

To find out if the concentration of parathyroid hormone-related protein (PTHrP) predicts the response of tumour-inducing hypercalcaemia (TIH) to pamidronate, we studied 44 patients. Pretreatment measurements of serum PTHrP, calcium and phosphate, nephrogenous cyclic AMP, tubular threshold for calcium and phosphate (TmP), and the presence of bone metastases were correlated with response to pamidronate. Response was considered good (normal calcium concentration corrected for albumin [CCa] for > 14 days), or poor (failure of CCa to fall, or a rise above normal < or = 14 days). PTHrP correlated significantly with response (good vs poor, p = 0.02). Undetectable PTHrP (< 2 pmol/L) was associated with a good response in all seven treatments, PTHrP in the range 2-12 pmol/L was associated with good response in 10 of 14 treatments, while PTHrP > or = 12 pmol/L was associated with a poor response in all 11 treatments. Tubular threshold for calcium correlated with the fall in CCa by day 6 after treatment (p = 0.02). Urinary clearance estimations in poor responders suggested that there was an incomplete reversal of the renal tubular component of hypercalcaemia. Serum PTHrP correlates with response to pamidronate in the treatment of TIH; which may be associated with a renal tubular mechanism not significantly affected by currently available treatment. Drugs that inhibit tubular reabsorption of calcium or PTHrP secretion may help in patients who do not respond to pamidronate.
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PMID:Parathyroid hormone-related protein and response to pamidronate in tumour-induced hypercalcaemia. 810 20

There is marked homology between the parathyroid hormone (PTH) and PTH-related protein (PTHrP) molecules at the amino terminal but the rest of the molecules are quite different, providing immunologically distinct peptides. However, they interact with the same receptor. Thus, PTHrP mediates biological actions reminiscent of PTH. PTHrP gene is a single copy gene, producing one to three mRNA transcripts through alternative splicing of the carboxy terminal, encoding peptides of 139, 141 or 173 amino acids. Having been recently isolated from malignant tumours, PTHrP is now considered to be the major mediator of humoral hypercalcaemia of malignancy (HHM). The PTH-like effects of PTHrP on the kidney and bone have been well characterized. The increase in renal tubular calcium reabsorption and the reduction in tubular phosphate reabsorption with a concomitant rise in nephrogenous cyclic AMP constitute the pathophysiological changes in the renal handling of calcium and phosphate in HHM. The osteotropic contribution to the malignant hypercalcaemia has been validated by enhanced osteoclastic bone resorption--an indirect effect of the amino terminal portion of the PTHrP molecule on osteoblasts. However, PTHrP has also been detected in a large number of normal adult tissues/organs as well as in human and animal fetuses. Fetal plasma calcium is higher than maternal and this is achieved by active transport of calcium across the placenta. Using ovine placental perfusion models, PTHrP, which is believed to originate from fetal parathyroid glands and the placenta itself, has been demonstrated to sustain this calcium gradient. Active placental transport of magnesium, but not phosphate, was also shown to be enhanced by PTHrP.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Parathyroid hormone-related protein and calcium phosphate metabolism. 813 Jan 17

Parathyroid hormone-related peptide (PTHrP) was originally isolated from tumors associated with the development of hypercalcemia in vivo. Analyses of PTHrP gene expression have demonstrated that PTHrP is also produced in a wide variety of normal fetal and adult nonneoplastic tissues. The results of recent experiments have demonstrated that PTHrP is a growth factor-regulated gene, and different molecular forms of synthetic PTHrP display variable activities in assays for growth factor-like properties in vitro. We have studied the growth factor-like activity of PTHrP in cells transfected with a human PTHrP (hPTHrP) expression vector. Transfected cell lines contained increased amounts of PTHrP mRNA transcripts as assessed by Northern blot analysis. The PTHrP mRNA transcripts were translated into immunoreactive hPTHrP as measured by radioimmunoassay, and conditioned medium from transfected cell lines stimulated cyclic AMP (cAMP) formation in ROS 17/2.8 osteosarcoma cells. The transforming growth factor-beta-like properties of hPTHrP-producing NRK 49F clones were examined using the large-colony transformation assay in soft agar. PTHrP-producing NRK 49F clones did not form large colonies in the presence of epidermal growth factor. In contrast, PTHrP-producing and wild-type NRK 49F cells formed large colonies in the presence of epidermal growth factor and transforming growth factor-beta. No effect on cell growth was observed in PTHrP-producing NRK 49F rat kidney fibroblasts or mouse NIH 3T3 fibroblasts. In contrast, RCB 2.2 osteoblast cells expressing the hPTHrP cDNA were growth inhibited. Incubation of wild-type RCB 2.2 cells with synthetic hPTHrP[1-34] (at concentrations of 1.0-10.0 nM) also produced growth inhibition. PTHrP increased cAMP formation in RCB 2.2 cells but not in NIH 3T3 or NRK 49F cells. Incubation of RCB 2.2 cells with dibutyryl cAMP was also associated with inhibition of cell growth. The results of these studies demonstrate that PTHrP may function as an autocrine growth inhibitor of specific cell types, possibly through a cAMP-dependent pathway.
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PMID:Growth factor-like properties of parathyroid hormone-related peptide in transfected rodent cell line. 831 5

We studied the influence of circulating parathyroid hormone-related protein (PTHrP) concentrations on the response of hypercalcemic cancer patients to bisphosphonate therapy. We also examined the changes in circulating PTHrP levels during the normalization of serum Ca to determine if part of the increase in PTHrP concentrations is not secondary to hypercalcemia itself, as suggested by some in vitro data. We sequentially measured in 45 hypercalcemic cancer patients treated by pamidronate the circulating concentrations of PTHrP (by an amino-terminal RIA; normal values < 9 pmol/liter), Ca, Ca2+, Pi, intact PTH, and the fasting urinary excretion of Ca (Ca/Cr) and cyclic AMP (cAMP). Mean +/- SEM baseline PTHrP levels were 9.5 +/- 1.3, with a median (range) value of 6.0 (< 3.4-43) pmol/liter. PTHrP levels were elevated in 18 of 45 patients, more often in epidermoid than in glandular carcinomas (P < 0.05), and they were significantly (P < 0.05) correlated with the concentrations of Pi (r = -0.46), Ca/Cr (r = -0.31), and urinary cAMP (r = 0.47). Mean pretreatment Ca levels were not significantly different between patients with elevated and patients with normal PTHrP levels, 13.3 +/- 0.4 versus 12.9 +/- 0.4 mg/dl, but the concentrations became significantly different (P < 0.005) 4 days after therapy, 10.2 +/- 0.3 versus 9.2 +/- 0.1 mg/dl, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Circulating PTHrP concentrations in tumor-induced hypercalcemia: influence on the response to bisphosphonate and changes after therapy. 832 12

The purpose of this study is to find out whether hypercalcemia and hyperparathyroidism are rare or not in manic-depressive patients taking lithium carbonate. The subjects were 13 patients receiving lithium and 19 healthy subjects not receiving it as normal controls. Serum ionized calcium (Ca++), serum parathyroid hormone (PTH), urinary calcium and cyclic AMP(cAMP) were measured. Cervical ultrasonographic examination was also performed. The mean serum Ca++ level in the lithium administered group was significantly higher than that in the control group (P < 0.02). There was no significant difference between the serum PTH levels in the two groups. The mean urinary calcium level in the lithium administered group was below the normal range, but the mean urinary of cAMP level was within the normal range. Although a parathyroid cyst was found in one lithium administered patient on ultrasonographic examination, no swelling of the parathyroid gland was observed in the other patients in the lithium administered group or in any of the control subjects. In the present study, no distinct hyperparathyroidism was found in the patients in the lithium administered group. Lithium administration affects calcium metabolism in manic-depressive patients and hypercalcemia seems to be one of the complications needing attention at the time of lithium administration.
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PMID:Effect of lithium on serum calcium level and parathyroid function in manic-depressive patients. 857 94


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